116 articles - From Saturday Jan 22 2022 to Friday Jan 28 2022
Guidelines, position statements, white papers, technical reviews, consensus statements, etc…
| Ann Oncol |
meta-analyses and systematic reviews
RCT, clinical trials, retrospective studies, etc…
| Am J Hematol |
A 29-gene signature associated with NOX2 discriminates acute myeloid leukemia prognosis and survival. In summary, we have found a gene signature (29G) that can be used for AML classification and for OS prediction. Our results confirm NOX and metabolism as suitable therapeutic targets in AML. |
Basiliximab for steroid-refractory acute graft-versus-host disease: A real-world analysis. Hence, we created a prognostic scoring system that could predict the risk of having a decreased likelihood of response after basiliximab treatment. Machine learning was used to develop a protocol that maximized the efficacy of basiliximab while maintaining acceptable levels of infection risk. Thus, real-world data suggest that basiliximab is safe and effective for treating SR-aGVHD. |
COVID-19 vaccines and risks of hematological abnormalities: nested case-control and self-controlled case series study. We observed an increased risk of leukopenia shortly after the second dose of BNT162b2. However, the incidence was much lower than the incidence following SARS-COV-2 infections. There was no association between CoronaVac and hematological abnormalities. The benefits of vaccination against COVID-19 still outweigh the risk of hematological abnormalities. |
Paroxysmal nocturnal hemoglobinuria and vascular liver disease: Eculizumab therapy decreases mortality and thrombotic complications. Six-year thrombosis-free survival was 70%, 95% CI [0.60-0.83] for PNH cohort and 83%, 95% CI [0.70-1.00] for non-PNH Envie 2 patients, (p |
Single-dose versus low-dose rituximab in corticosteroid-resistant or relapsed ITP: A multicenter, randomized, controlled study. The single-dosage regimen optimizes the use of medical resources, improves the cost-effectiveness of RTX, and represents a promising and more convenient replacement for LD-RTX in ITP. This study has been completed and is registered with ClinicalTrials. gov, number NCT03258866. |
| Ann Oncol |
Comprehensive assessment of germline pathogenic variant detection in tumor-only sequencing. Tumor-only sequencing is adequate for the detection of clinically actionable germline variants, particularly for SNVs and small indels; however, a small subset of alterations affecting HRD, DDR and MMR genes may not be detected optimally. Therefore, for high-risk patients with negative tumor-only sequencing results, clinical genetic testing could be considered given the impact of these variants on therapy and genetic counseling. |
Single cell DNA-seq depicts clonal evolution of multiple driver alterations in osimertinib resistant patients. Distinct molecular driver alterations at osimertinib resistance co-exist with initial EGFR mutations in single cancer cells. The clonal evolution of cancer cell populations emphasized their heterogeneity leading to osimertinib relapse. Combining two targeted treatments is effective to achieve clinical benefit. |
| Blood |
CRLF3 plays a key role in the final stage of platelet genesis and is a potential therapeutic target for thrombocythaemia. We show that Crlf3-/- preplatelets have increased microtubule stability, possibly due to increased microtubule glutamylation via CRLF3's interaction with key members of the Hippo pathway. Using a mouse model of JAK2V617F Essential Thrombocythaemia (ET), we show that a lack of CRLF3 leads to a long-term lineage-specific normalisation of the platelet count. We thereby postulate that targeting CRLF3 has therapeutic potential for treatment of thrombocythaemia. |
Early intestinal microbial features are associated with CD4 T cell recovery after allogeneic hematopoietic transplant. We observed that fecal microbial diversity was an independent predictor of CD4 T cell count 3 months after HCT in recipients of a CD34-selected allograft, who are dependent on de novo lymphopoiesis for their immune recovery. In multivariate models using clinical factors and microbiota features, we consistently observed that increased fecal relative abundance of genus Staphylococcus during the early post-transplant period was associated with worse CD4 T cell recovery. Our observations suggest that the intestinal bacteria - or the factors they produce - can affect early lymphopoiesis and the homeostasis of allograft-derived T cells after transplantation. |
PI3Kd/ After transfer to NOG mice engrafted with a human CLL cell line, Duv-CART cells expressing either a CD28 or 41BB costimulatory domain demonstrated significantly increased in vivo expansion of CD8+ CART cells, faster elimination of CLL, and longer persistence. Duv-CART cells significantly enhanced survival of CLL-bearing mice compared with conventionally manufactured CART cells. In summary, exposure of CART to a PI3Kd/ |
Severely impaired CTL killing is a feature of the neurological disorder Niemann-Pick Syndrome type C1. We demonstrated defects of CTL function of varying severity in NP-C1 patients, with the greatest loss of function associated with the most florid and/or earliest disease presentations. Remarkably, perforin function and CTL cytotoxicity were restored in vitro by promoting lipid clearance with therapeutic 2-hydroxypropyl-b-cyclodextrin (HPbCD), whereas restoring autophagy through TFEB over-expression was ineffective. Overall, our study revealed that NPC1 deficiency has a deleterious impact on CTL (but not natural killer cell) cytotoxicity that, in the long term, may predispose NP-C1 patients to atypical infections and impaired immune surveillance more generally. |
Structural Racism is a Mediator of Disparities in Acute Myeloid Leukemia Outcomes. Strikingly, census tract measures accounted for nearly al of the NHB-NHW and Hispanic-NHW disparity in leukemia death. Treatment patterns, including induction intensity and allogeneic transplant, as well as treatment complications, as assessed by ICU admission during induction chemotherapy, were additional mediators of survival disparities in AML. This is the first study to formally test mediators for observed disparities in AML survival and highlights the need to investigate the mechanisms by which structural racism interacts with known prognostic and treatment factors to influence leukemia outcomes. |
Three FDA-approved therapies for chronic GVHD. Chronic GVHD involves multiple organs, reduces quality of life and often requires prolonged therapy with glucocorticoids, causing severe side effects. After four decades of testing multiple therapeutic approaches, the drugs ibrutinib, belumosudil and ruxolitinib were FDA-approved for cGVHD in the last four years. Here we put a spotlight on their mechanisms of action, the studies that led to approval, and their future role in cGVHD. |
Unique molecular and functional features of extramedullary hematopoietic stem and progenitor cell reservoirs in humans. Finally, the unique erythroid-megakaryocytic-skewing of PB is perturbed with age, in essential thrombocythemia and in beta-thalassemia. Collectively, we identify extramedullary lineage-primed HSPC reservoirs that are non-proliferative in situ and report involvement of splenic HSPCs during demand-adapted hematopoiesis. Our data also establish aberrant composition and function of circulating HSPCs as potential clinical indicators of BM dysfunction. |
| Blood Adv |
A Model for Surface-Dependent Factor XII Activation: The Roles of Factor XII Heavy Chain Domains. This interaction is disrupted by the lysine analog |
Analysis of Preplatelets and Their Barbell Platelet Derivatives by Imaging Flow Cytometry. Furthermore, barbells were absent post-chemotherapy in patients. In mice, in vivo biotinylation confirmed that barbells, but not al large platelets, were immature. This study demonstrates that a subpopulation of large platelets are immature preplatelets that can transform into barbells and undergo fission during maturation. |
Anti-platelet medications and risk of intracranial hemorrhage in patients with metastatic brain tumors. Cumulative incidence of major ICH was 5.4% (95% CI, 2.6-8.3%) among controls compared with 5.5% (95% CI, 1.5-9.5%, P=0.80) in those exposed to antiplatelet agents. The combination of anticoagulation with antiplatelet agents did not increase the risk of major ICH. The use of antiplatelet agents was not associated with an increase in the incidence, size, or severity of ICH in the setting of brain metastases. |
Associating Drug Sensitivity with Differentiation Status Identifies Effective Combinations for Acute Myeloid Leukemia. Enrichment for DORA and VEN sensitivities were observed in AML with monocyte-like and progenitor-like transcriptomic signatures, respectively, and these associations diminished with the combination. The mechanism underlying the combination's enhanced efficacy may result from inhibition of p38 MAPK-mediated phosphorylation of BCL2, which in turn enhances sensitivity to venetoclax. These findings suggest exploiting complementary drug sensitivity profiles with respect to leukemic differentiation state, such as dual targeting of p38 MAPK and BCL2, offers opportunity for broad, enhanced efficacy across the clinically challenging heterogeneous landscape of AML. |
Benefits of Newborn Screening and Hematopoietic Cell Transplant in Infantile Krabbe Disease. All children are alive and have derived developmental and neurologic benefits from timely HCT. Long-term follow up is ongoing. Optimization of HCT and further development of emerging therapies, al of which must be delivered early in life, are expected to further improve outcomes of infants with IKD. |
Characteristics and Outcomes of Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm Treated with Frontline HCVAD. HSCT was performed in 51% vs 49% vs 38% respectively (p=0.455). These results suggest a continued important role for HCVAD-based chemotherapy for BPDCN, even in the modern targeted-therapy era, with high CR rates in the frontline setting. Further studies must establish the clinical activity, feasibility, and safety, of doublet/triplet combinations of targeted therapies plus cytotoxic agents and addition of CNS prophylaxis, with ultimate goal of durable long-term remissions for patients with BPDCN. |
Differential impact of tamoxifen and aromatase inhibitors on thrombin generation: the prospective HEMOBREAST cohort. The observed shift towards increased coagulability associated with tamoxifen is in line with its known increased risk of VTE. In contrast, AIs do not appear to impact hemostasis, suggesting a lack of associated VTE risk. |
Eculizumab for Refractory Thrombosis in Antiphospholipid Syndrome. Following this event, eculizumab (600mg weekly x 4 weeks followed by 900mg every 2 weeks) was initiated in combination with fondaparinux, aspirin, clopidogrel and hydroxychloroquine. She has remained on this regimen without recurrence of thrombosis. Our case suggests that eculizumab may have a role as a therapeutic option in refractory thrombosis in APS. |
Four AAs increase DMT1 abundance in duodenal brush-border membrane vesicles and enhance iron absorption in iron-deprived mice. Additional experimentation suggested that intestinal DMT1 was required for enhancement of iron transport by the 4AAs. Select AA thus enhance iron absorption by inducing DMT1 trafficking onto the apical membrane of duodenal enterocytes. We speculate that further refinement of this new 4AA formulation will ultimately allow iron repletion at lower effective doses (thus mitigating negative side effects of excess enteral iron). |
Incidence and time trends of second primary malignancies after non-Hodgkin lymphoma: a Swedish population-based study. We conclude that NHL survivors have an increased risk of both solid tumors and hematologic malignancies, in particular MDS/AML. Stable excess risks over time indicate that contemporary treatment standards are not associated with modified SPM risk. Encouragingly, decreasing rates of MDS/AML were noted among patients with follicular lymphoma, possibly due to increasing use of non-chemotherapy-based treatments. |
IRF8 is a transcriptional activator of CD37 expression in diffuse large B-cell lymphoma. Functional analysis indicated that IRF8 overexpression enhanced CD37 protein expression, while CRISPR/Cas9 knock-out of IRF8 decreased CD37 levels in DLBCL cell lines. Immunohistochemical analysis in a large cohort of primary DLBCL (n=206) revealed a significant correlation of IRF8 expression with detectable CD37 levels. Together, this study provides new insight into the molecular mechanisms underlying differential CD37 expression in human DLBCL, and reveals IRF8 as transcriptional regulator of CD37 in B-cell lymphoma. |
Lupus anticoagulant test persistence over time and its associations with future thrombotic events. Vitamin K antagonist (VKA) treatment at baseline was associated with a negative LA test during follow up. Using a multistate time-to-event model with multivariable adjustment, a negative LA test had no impact on a patient's prospective risk of thrombosis or mortality. We conclude that a negative LA test during observation cannot be used clinically to stratify a patient's risk for future events. |
Management Strategies Following Slightly Out of Range INRs: Watchful Waiting vs. Dose Changes. The next INR was slightly less likely to be in range with watchful waiting than with a dose change (Predicted Probabilities 58.9% vs 60.0%, P-value = 0.024). Although a significant statistical difference was detected in the probabilities of the next INR being back in range when managed by a dose change compared to watchful waiting following a slightly out of range INR, the magnitude of the difference was small and unlikely to represent clinical importance. Our study supports the current guideline recommendations for watchful waiting in cases of slightly out of range INRs values. |
MicroRNA-31 regulates T-cell metabolism via HIF1a and promotes chronic GVHD pathogenesis in mice. Importantly, systemic administration of a specific inhibitor of miR-31 effectively reduced donor T-cell expansion, improved Treg generation, and attenuated cGVHD. Taken together, miR-31 is a key driver for T-cell pathogenicity in cGVHD but not for the anti-leukemia activity. Taken together, miR-31 is essential to drive cGVHD pathogenesis and represents a novel potential therapeutic target for controlling cGVHD. |
Neurofilament light chain serum levels correlate with the severity of neurotoxicity after CAR T cell treatment. Pre-existing neuroaxonal injury, characterized by higher NfL levels before CAR T-cell treatment, correlated with the severity of subsequent ICANS. Thus, serum NfL level might serve as a predictive biomarker for assessing the severity of ICANS and for improving patient monitoring following CAR T-cell transfusion. However, these preliminary results should be validated in a larger prospective cohort of patients. |
Outcomes of Relapsed B-Cell Acute Lymphoblastic Leukemia After Sequential Treatment with Blinatumomab and Inotuzumab. Overall survival (OS) was not different between alloHCT and non-alloHCT patients. In conclusion, patients with B-ALL who relapsed after blinatumomab could be successfully rescued by inotuzumab as a bridge to alloHCT, but represent an ultra-high risk group with poor OS. Further studies including novel consolidation and treatment sequence may improve outcomes of these patients. |
Patient-specific MDS-RS iPSCs define the mis-spliced transcript repertoire and chromatin landscape of SF3B1-mutant HSPCs. Transcription factor motifs enriched in chromatin regions more accessible in SF3B1K700E cells included, unexpectedly, motifs of the TEAD family. TEAD expression and transcriptional activity were upregulated in SF3B1-mutant iPSC-HSPCs, in support of a Hippo pathway-independent role of TEAD as a potential novel transcriptional regulator of SF3B1K700E cells. This study provides a comprehensive characterization of the transcriptional and chromatin landscape of SF3B1K700E HSPCs and nominates novel mis-spliced genes and transcriptional programs with putative roles in MDS-RS disease biology. |
Prediction of Life-threatening and Disabling Bleeding in Patients with AML Receiving Intensive Induction Chemotherapy. Cumulative incidence of grade 4 bleeding at day+60 was significantly higher among patients with high- versus low-risk (development: 31+7% vs 2+1%, P<0.001, validation: 25+9% vs 7+2%, P=0.008). In both cohorts, high bleeding risk was associated with disseminated intravascular coagulation (DIC) and proliferative disease. We developed and validated a simple risk model for grade 4 bleeding, which enables development of rational risk mitigation strategies to improve early mortality of intensive induction treatment. |
Reduced intensity hematopoietic stem cell transplantation for myelofibrosis in accelerated-phase. Results were confirmed in multivariable analysis and propensity score matching. Increase in circulating blasts was associated with increased risk for relapse, showing strongest increase in risk for =10% blasts. In conclusion, reduced intensity transplantation showed excellent survival but higher relapse for AP myelofibrosis. |
Risk profiling of patients with relapsed/refractory diffuse large B-cell lymphoma by measuring circulating tumor DNA. Baseline ctDNA assessment may identify patients at high risk of progression, and should be further evaluated as a monitoring tool in R/R DLBCL. ClinicalTrials. gov identifier: NCT02257567. |
SFPQ-ABL1 and BCR-ABL1 utilize different signalling networks to drive B-cell acute lymphoblastic leukaemia. SFPQ-ABL1 expression did not activate PI3K/AKT signalling and was associated with phosphorylation of G2/M cell cycle proteins. SFPQ-ABL1 was sensitive to navitoclax and S-63845 and promotes cell survival by maintaining expression of Mcl-1 and Bcl-xL. SFPQ-ABL1 has functionally distinct mechanisms by which it drives ALL, including subcellular localisation, proliferative capacity, and activation of cellular pathways, highlighting the role that fusion partners have in mediating the function of ABL1 fusions. |
Structure of shear-induced platelet aggregated clot formed in an in vitro arterial thrombosis model. The results reveal a complex structure of arterial thrombi that grow from their tips under high shear stress to bridge the 2.5 mm lumen quickly with VWF-platelet strings. The occlusion leaves many microchannels that allow some flow through the bulk of the thrombus. This architecture can create occlusion or hemostasis rapidly with minimal material, yet remain porous for potential delivery of lytic agents to the core of the thrombus. |
The ASH-ASPHO Choosing Wisely Campaign: 5 hematologic tests and treatments to question. By using an iterative process and an evidence-based method, the ASH-ASPHO Task Force identified 5 hematologic tests and treatments that health care providers and patients should question because they are not supported by evidence, and/or they involve risks of medical and financial costs with low likelihood of benefit. The ASH-ASPHO Choosing Wisely recommendations are as follows: (1) avoid routine preoperative hemostatic testing in an otherwise healthy child with no previous personal or family history of bleeding, (2) avoid platelet transfusion in asymptomatic children with a platelet count >10 |
TP53 mutation defines a unique subgroup within complex karyotype de novo and therapy-related MDS/AML. Multivariable analysis identified presence of multi-hit TP53 mutation as strongest predictor of worse outcome, while neither a diagnosis of AML versus MDS nor therapy-relatedness independently influenced OS. Our findings suggest that among patients with MDS and AML, the presence of TP53 mutation (in particular multi-hit TP53 mutation) in the context of CK identifies a homogeneously aggressive disease, irrespective of the blast count at presentation or therapy-relatedness. The current classification of these cases into different disease categories artificially separates a single biologic disease entity. |
Validation of the Khorana score for predicting venous thromboembolism in 40 218 cancer patients initiating chemotherapy. In conclusion, the Khorana score was able to stratify ambulatory cancer patients according to risk of venous thromboembolism, but not for al cancer types. Absolute risks varied by methodology but were lower than in key randomized trials. Thus, although certain limitations with outcome identification using administrative registries apply, the absolute benefit of implementing routine primary thromboprophylaxis in an unselected cancer population may be smaller than seen in randomized trials. |
| Blood Cancer J |
Clinico-biological features of T-cell acute lymphoblastic leukemia with fusion proteins. The clinico-biological characteristics linked to fusion transcripts in a subset of 235 patients (138 adults in the GRAALL2003/05 trials and 97 children from the FRALLE2000 trial) were analyzed to identify their prognosis impact. Patients with HOXA trans-deregulated T-ALLs with MLLT10, KMT2A and SET fusion transcripts (17%, 39/235) had a worse prognosis with a 5-year EFS of 35.7% vs 63.7% (HR |
Clonal and subclonal TP53 molecular impairment is associated with prognosis and progression in multiple myeloma. Moreover, the analysis of longitudinal samples pointed out that TP53 allelic status might increase during the disease course. Notably, the acquisition of TP53 alterations at relapse dramatically worsened the clinical course of patients. Overall, our analyses showed these techniques to be highly sensitive to identify TP53 aberrations at sub-clonal level, emphasizing the poor prognosis associated with double-hit MM patients. |
Oral ixazomib-dexamethasone vs oral pomalidomide-dexamethasone for lenalidomide-refractory, proteasome inhibitor-exposed multiple myeloma: a randomized Phase Ixa-dex represents an important lenalidomide-free, oral option for this heavily pretreated, lenalidomide-refractory, proteasome inhibitor-exposed population. Trial registration: ClinicalTrials. gov number, NCT03170882. |
Patterns of neutralizing humoral response to SARS-CoV-2 infection among hematologic malignancy patients reveal a robust immune response in anti-cancer therapy-naive patients. Enhanced serum neutralizing activity was observed in the following SARS-CoV-2-infected HM patient groups: (i) males; (ii) severe COVID-19; and (iii) "watch and wait" or "complete/partial response". The geometric mean (GeoMean) ID50 neutralization titers in patients analyzed before or after 6 months post-infection were 299.1 and 306.3, respectively, indicating that >50% of the patients in either group had a neutralization titer sufficient to provide 50% protection from symptomatic COVID-19. Altogether, our findings suggest that therapy-naive HM patients mount a far more robust immune response to SARS-CoV-2 infection vs patients receiving anti-cancer treatment, raising the important question as to whether HM patients should be vaccinated before therapy and/or receive vaccine formats capable of better recapitulating the natural infection. |
| Haematologica |
A real-world based score to predict early death in acute promyelocytic leukemia. The score identified an increased risk of ED already at sub-normal and normal WBC levels and consequently, it was better to predict ED risk than the Sanz score (AUROC 0.77 vs 0.64). In summary, we here present an externally validated and population-based risk score to predict ED risk in a real-world setting, identifying patients with the most urgent need of aggressive ED prevention. Also, the results suggest increased vigilance for ED already at sub-normal/normal WBC levels. |
Comprehensive genomic analysis of refractory multiple myeloma reveals a complex mutational landscape associated with drug resistance and novel therapeutic vulnerabilities. We observed a major impact of signatures associated with exposure to melphalan or impaired DNA double-strand break homologous recombination repair in RRMM. The latter coincided with mutations in genes associated with PARP inhibitor sensitivity in 49% of RRMM patients, a finding with potential therapeutic implications. In conclusion, this comprehensive genomic characterization revealed a complex mutational and structural landscape in RRMM and highlights potential implications for therapeutic strategies. |
Programmed cell death ligand 1 expression in aggressive pediatric non-Hodgkin lymphomas: frequency, genetic mechanisms, and clinical significance. Overexpressed PD-L1 is common in pediatric LBCL, associated with EBV-positivity and 9p24.1 gains, and may have prognostic significance in de novo LBCL. Furthermore, diverse molecular mechanisms for PD-L1 overexpression in aggressive pediatric NHL can occur. Thus, additional studies exploring the therapeutic and prognostic significance and molecular mechanisms of PD-L1 overexpression in aggressive pediatric NHLs are warranted. |
Syntaxin 5 determines Weibel-Palade body size and Von Willebrand factor secretion by controlling Golgi architecture. STX5-depleted ECs exhibited extensive Golgi fragmentation and decreased WPB length, which was associated with reduced intracellular VWF levels, and impaired stimulated VWF secretion. However, the secretionincompetent organelles in shSTX5 cells maintained WPB markers such as Angiopoietin 2, Pselectin, Rab27A, and CD63. Taken together, our study has identified SNARE protein STX5 as a novel regulator of WPB biogenesis. |
The mitochondrial anti-apoptotic dependencies of hematological malignancies: from disease biology to advances in precision medicine. In this review, we highlight the rationale of targeting mitochondrial apoptosis in hematology, and provide a comprehensive map of the antiapoptotic dependencies that are currently guiding novel therapeutic strategies. Cell-extrinsic and intrinsic mechanisms conferring resistance to BH3 mimetics are also examined, with insights on potential strategies to overcome them. We finally discuss how the field of mitochondrial apoptosis might be complemented with other dimensions of precision medicine for more successfully treating 'highly complex' hematological malignancies. |
| Leukemia |
Combination therapy targeting Erk1/2 and CDK4/6i in relapsed refractory multiple myeloma. Our studies showed that Erk1/2i |
| Thromb Haemost |
Associations between the von Willebrand Factor-ADAMTS13 Axis, Complement Activation, and COVID-19 Severity and Mortality. Our results suggest that an interaction between the VWF-ADAMTS13 axis and complement overactivation and consumption plays an important role in the pathogenesis of COVID-19. |
Impact of fibrinogen infusion on thrombin generation and fibrin clot structure in patients with inherited afibrinogenemia. In summary, fibrinogen infusion with a standard dose of FC increased but did not correct TG and led to formation of fibrin clots similar to those of patients with hypofibrinogenemia. All in all, our results do not support to biological evidence of hypercoagulability induced by FC in patients with afibrinogenemia. |
Novel GNE Gene Variants Associated with Severe Congenital Thrombocytopenia and Platelet Sialylation Defect. Lectin array showed decreased a-2,3-sialylation on platelets, consistent with loss of sialic acid synthesis and indicative of rapid platelet clearance. Hematopoietic stem cell transplantation (HSCT) normalized platelet counts. This is the first report of an HSCT in a patient with an inherited GNE defect leading to normal platelet counts. |
Stroke and Thromboembolism in Patients with Heart Failure and Sinus Rhythm: A Matter of Risk Stratification? The challenge is to adequately identify this subgroup and to balance the potential benefit of anticoagulation with the risk of major bleeding. There is also an unmet need for evidence around anticoagulation in HF with preserved ejection fraction (HFpEF) and SR. This review explores the current evidence around anticoagulation in patients with HF and SR, identifies challenges regarding outcome definitions and patient selection, and offers suggestions for future research. |
Plenty of the editorials are available as full text through the publisher website using the provided link
| Ann Oncol |
| Blood |
| Blood Cancer J |
JAK2 inhibitor persistence in MPN: uncovering a central role of ERK activation. These approaches include, among others, phosphoproteomic analyses of JAK2 signaling as well as detailed assessment of JAK2 inhibition in mouse models of MPN. In this focused review, we highlight these and other studies that collectively suggest targeting MEK/ERK in combination with JAK2 inhibition has the potential to improve the efficacy of JAK2 inhibitors in MPN patients. As MPN patients patiently wait for improved therapies, such studies should further strengthen optimism that pre-clinical research is continuing to uncover mechanistic insights regarding the ineffectiveness of JAK2 inhibitors, which may lead to development of improved therapeutic strategies. |
| J Hematol Oncol |
Momelotinib: an emerging treatment for myelofibrosis patients with anemia. Momelotinib is one of the prime candidates to durably address the critical unmet needs of MF patients with moderate/severe anemia. Importantly, momelotinib may have overall survival benefits in frontline and second-line MF patients. MOMENTUM is an international registration-track phase 3 trial further assessing momelotinib's unique constellation of anemia and other benefits in second-line MF patients; the results of the MOMENTUM trial are keenly awaited and may lead to regulatory approval of momelotinib may lead to its approval. |
RNA demethylase ALKBH5 in cancer: from mechanisms to therapeutic potential. Meanwhile, increasing non-coding RNAs are recognized as functional targets of ALKBH5 in cancers. Here we reviewed up-to-date findings about the pathological roles of ALKBH5 in cancer, the molecular mechanisms by which it exerts its functions, as well as the underlying mechanism of its dysregulation. We also discussed the therapeutic implications of targeting ALKBH5 in cancer and potential ALKBH5-targeting strategies. |
Targeting PARP proteins in acute leukemia: DNA damage response inhibition and therapeutic strategies. Despite the low frequency of genomic alterations of PARP and other DDR-related genes in acute leukemia, selective vulnerabilities have been reported in several disease subgroups, along with a "BRCAness phenotype." AML carrying the RUNX1-RUNX1T1 or PML-RARA fusion genes or mutations in signaling genes (FLT3-ITD in combination with TET2 or TET2 and DNMT3A deficiency), cohesin complex members (STAG2), TP53 and BCOR as co-occurring lesions, IDH1/2 and ALL cases expressing the TCF3-HLF chimera or TET1 was highly sensitive to PARPi in preclinical studies. These data, along with the warning coming from the observation of cases of therapy-related myeloid malignancies among patients receiving PARPi for solid tumors treatment, indicate that PARPi represents a promising strategy in a personalized medicine setting. The characterization of the clonal and subclonal genetic background and of the DDR functionality is crucial to select acute leukemia patients that will likely benefit of PARPi-based therapeutic regimens. |
| Leukemia |
Letters to the editors and authors’ replies
| Am J Hematol |
| Ann Oncol |
| Blood Adv |
| Blood Cancer J |
| J Hematol Oncol |
Development of a novel combined nomogram model integrating deep learning-pathomics, radiomics and immunoscore to predict postoperative outcome of colorectal cancer lung metastasis patients. The combined nomogram showed outstanding performance in predicting OS (AUC |
High familial burden of cancer correlates with improved outcome from immunotherapy in patients with NSCLC independent of somatic DNA damage response gene status. The prevalence of |
| Leukemia |
all remaining publications eg case reports, images of the month, etc…
| Am J Hematol |
| Blood |
| Blood Adv |
| CA Cancer J Clin |
| Leukemia |
| Thromb Haemost |